☆ 4.3 Editorial Material

Role of the PD-1 and PD-L1 axis in COVID-19

FUTURE MICROBIOLOGY (2022)

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Summary: Severe COVID-19 is associated with systemic inflammation and progressive dysfunction of CD4(+) T cells. Platelets from COVID-19 patients contribute to this dysfunction by inhibiting the upregulation of CD25 expression and tumor necrosis factor (TNF)-alpha production, and decreasing interferon (IFN)-gamma production by CD4(+) T cells. Additionally, platelets from COVID-19 patients exhibit a high expression of PD-L1, which inversely correlates with IFN-gamma production by activated CD4(+) T cells co-cultured with platelets. A PD-L1-blocking antibody can restore platelets' ability to stimulate IFN-gamma production by CD4(+) T cells.

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Comprehensive Immune Profiling Reveals CD56+ Monocytes and CD31+ Endothelial Cells Are Increased in Severe COVID-19 Disease

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Summary: Immune response dysregulation plays a key role in the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The study evaluated immune and endothelial blood cell profiles of COVID-19 patients, revealing depletion of T cell subsets and an increase in CD56(+) monocytes in severe cases. Age, obesity, and hypertension were found to synergistically impact immune markers and disease severity in SARS-CoV-2 infection.

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SARS-CoV-2 Induces Cytokine Responses in Human Basophils

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Summary: This study reports that SARS-CoV-2 induces cytokine responses, particularly IL-13, in both resting and IL-3 primed basophils. However, the expression of surface markers associated with basophil activation and PD-L1 expression on basophils are not affected by SARS-CoV-2. The results suggest that basophil cytokine responses to SARS-CoV-2 might help reduce inflammation and promote antibody responses to the virus.

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IFN-γ Induces PD-L1 Expression in Primed Human Basophils

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Circulating Levels of PD-L1, TIM-3 and MMP-7 Are Promising Biomarkers to Differentiate COVID-19 Patients That Require Invasive Mechanical Ventilation

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Summary: This study aimed to evaluate the disease severity of COVID-19 patients and identify potential biomarkers. The results showed that the levels of sPD-L1, sTIM-3, and sMMP-7 were associated with patients requiring invasive mechanical ventilation (IMV). Additionally, sMMP-7 could be a marker for the persistence of lung lesions post-COVID-19.

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Impaired function and delayed regeneration of dendritic cells in COVID-19

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PD-1 blockade counteracts post-COVID-19 immune abnormalities and stimulates the anti-SARS-CoV-2 immune response

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Summary: A significant proportion of COVID-19 recovered patients exhibit altered immune characteristics, with exhausted T cells and dysfunctional immune responses, including a poor reaction to viral antigens. Immune checkpoint blockade can ameliorate these post-COVID-19 immune abnormalities and enhance anti-SARS-CoV-2 immune responses.

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PD-L1 Dysregulation in COVID-19 Patients

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Summary: The COVID-19 pandemic has led to severe social and medical consequences, including a subset of patients with rapidly worsening severe-critical manifestations. Prognostic biomarkers and therapeutic approaches are urgently needed to address this issue. Dysregulated immune response, particularly involving immune checkpoint molecules like PD-1 and PD-L1, play a significant role in COVID-19 pathogenesis. Serum levels of PD-L1 have shown to have a prognostic role in COVID-19 patients, indicating the potential for PD-1/PD-L1 inhibitors in clinical studies.

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Severe COVID-19 Recovery Is Associated with Timely Acquisition of a Myeloid Cell Immune-Regulatory Phenotype

Amelia C. Trombetta et al.

Summary: This study found that the acquisition of an immune-regulatory myeloid cell phenotype may contribute to recovery in severe COVID-19 patients, and therapeutic agents favoring an innate immune system regulatory shift could be the best strategy at this stage.

FRONTIERS IN IMMUNOLOGY (2021)

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Review Oncology

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

Christian Bailly et al.

Summary: This study highlights the biochemical and functional heterogeneity of soluble PD-L1 (sPD-L1) isoforms, generated by proteolysis or alternative splicing, and its role beyond cancer in various diseases and conditions such as inflammatory diseases and pregnancy.

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Disharmonic Inflammatory Signatures in COVID-19: Augmented Neutrophils' but Impaired Monocytes' and Dendritic Cells' Responsiveness

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Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19

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Interleukin-10 determines viral clearance or persistence in vivo

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PD-L2 is a second ligand for PD-I and inhibits T cell activation

Y Latchman et al.

NATURE IMMUNOLOGY (2001)

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